PrEP-Related Bone Density Loss Most Concerning Among Young MSM, Study Says


A recent study found some improvement in bone density after PrEP discontinuation along with some lingering concerns, particularly among the youngest participants.

The effects of HIV pre-exposure prophylaxis (PrEP) on bone mineral density (BMD) have been a topic of ongoing study. A new study involving young men who have sex with men that aimed to determine whether a loss of BMD reverses after discontinuation of the treatment revealed some improvement with some lingering concerns, particularly among the youngest participants.

The study, published in the journal Clinical Infectious Diseases, examined data from 2 open-label studies of tenofovir disoproxil fumarate with emtricitabine (TDF/FTC) given once orally for 48 weeks. Study participants included men ages 15-22 years and the investigators measured BMD and bone mineral content (BMC) at baseline, 24 and 48 weeks by dual-energy X-ray absorptiometry, at lumbar spine, total hip and whole body.

The study found partial or full BMD recovery 48 weeks after discontinuation of PrEP, with lumbar spine and whole-body BMD Z scores remained below baseline for those ages 15-19 years.

“No fractures have been associated with TDF use for PrEP, so maybe the finding of lower bone mineral density is not too concerning from a clinical perspective,” corresponding author Peter L. Havens, MD, MS, professor of pediatrics at the Medical Center of Wisconsin, told Contagion®. “We found an abnormal test (DXA scan). We did not find a disease (there were not any bone fractures).”

“However, in youth, bone growth continues into young adulthood, so low BMD might alter ‘peak bone mass,’ which could be associated with fractures in later life,” Havens continued. “This remains speculative. PrEP prevents HIV acquisition, so a small theoretical risk of later fracture is clearly balanced by the immediate protection from HIV infection offered by TDF.”

More studies are needed to examine reasons for variability and possible factors such as vitamin D deficiency, use of amphetamines and being underweight.

“Physicians could consider giving vitamin D to recipients of TDF-containing PrEP,” Havens told Contagion®. “This should be vitamin D3 and can be given as 1000 or 2000 IU daily or 10,000 IU weekly or 50,000 IU once a month.”

The study noted that vitamin D deficiency was associated with bone toxicity and that high vitamin D3 doses may reverse or mitigate bone loss in people infected with HIV.

The effects of PrEP on BMD have been investigated in previous studies.

A recent study, published online in the journal AIDS Research and Human Retroviruses, also found a slight loss of mineral bone density with the use of PrEP containing tenofovir. Noting that the declines were likely clinically significant only for those at the highest risk of bone toxicity, the study authors recommended that those at high risk of bone fracture consider other alternatives, such as tenofovir alafenamide‐based PrEP once available or dose‐limiting strategies. They also supported further study into recommending calcium and vitamin D supplements before starting PrEP.

An earlier study at the University of Alabama Birmingham School of Public Health involving adolescents had similar results, finding a loss in bone mineral density among those taking PrEP. That study also noted recovery of bone density after discontinuation of the treatment.

The US Food and Drug Administration approved TDF/FTC for use among adolescents last year, noting the possibility of modest decreases in bone mineral density.

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